SENSITIVITY OF PEPTIDE CONFORMATION TO METHODS AND GEOMETRICAL PARAMETERS - A COMPARATIVE ABINITIO AND MOLECULAR MECHANICS STUDY OF OLIGOMERS OF ALPHA-AMINOISOBUTYRIC-ACID

The conformational behavior of α-aminoisobutyric acid has been investigated by means of ab initio and empirical methods. Empirical computations performed with fixed bond lengths and valence angles using well-known force fields show that C5, C7, and helical structures correspond to energy minima, but the relative stability of different conformers is strongly dependent on the parametrization. Ab initio computations performed to solve these discrepancies suggest that the three structures are essentially isoenergetic. An alternative set of net charges significantly improves the agreement between ab initio and molecular mechanics results. Complete geometry optimization using both ab initio and empirical methods does not affect the relative stabilities of C5 and C7 structures but significantly destabilizes the helical one. Zero point and entropy effects, although slightly destabilizing the C7 structure, do not alter this general trend. The stabilization of helical structures with respect to C5 and, especially, C7 ones in polar solvents has been recovered by varying the dielectric constant governing intramolecular electrostatic interactions. Computations performed for oligomers of alanine and α-aminoisobutyric acid up to the octamer confirm the faster onset of helical structures for α-aminoisobutyric acid evidenced by experimental observations. © 1990, American Chemical Society. All rights reserved.